Vinyl Boronates Research Articles

Formation of C(sp(2))-boronate esters by borylative cyclization of alkynes using BCl3.

BCl3 is an inexpensive electrophile which induces the borylative cyclization of a wide range of substituted alkynes to regioselectively form polycycles containing synthetically versatile C(sp2)—boronate esters. It proceeds rapidly, with good yields and is compatible with a range of functional groups and substitution patterns. Intermolecular 1,2‐carboboration of alkynes is also achieved using BCl3 to generate trisubstituted vinyl boronate esters.

Synthesis of Vinyl Boronates

Synthesis of Vinyl Boronates

Stereo- and Regioselective Formation of Silyl-Dienyl Boronates.

The intramolecular trans-silylruthenation of internal alkynes and subsequent insertion of vinyl boronates is described. This approach provides complete regiocontrol through a stereoselective trans-5-exo-dig cyclization which affords a tetrasubstituted olefin as a vinylsilane and a highly functionalized Z,E diene motif.

Organocatalytic asymmetric C-H vinylation and arylation of N-acyl tetrahydroisoquinolines.

The first organocatalytic enantioselective oxidative C-H functionalization of N-acyl tetrahydroisoquinolines with vinyl and aryl boronates promoted by a chiral Brønsted acid is described. This metal-free process tolerates a wide range of electronically varied N-acyl tetrahydroisoquinolines and structurally diverse boronates with good to excellent enantioselectivities.

Synthesis of vinyl boronates from aldehydes by a practical boron-Wittig reaction.

A highly stereoselective boron-Wittig reaction between stable and readily accessible 1,1-bis(pinacolboronates) and aldehydes furnishes a variety of synthetically useful di- and trisubstituted vinyl boronate esters.

Regio- and Chemoselective Diboration of Allenes with Unsymmetrical Diboron: Formation of Vinyl and Allyl Boronic Acid Derivatives

A platinum-catalyzed terminal diboration of 1,1-disubstituted allenes using a differentially protected diboron is described. Diboration occurs in a regio- and chemoselective fashion to furnish vinyl and allyl boronates in good to excellent yield and selectivity. Transformation of the bis-boronyl products to other functional groups as well as in chemoselective cross-coupling is demonstrated.

ChemInform Abstract: Palladium‐Catalyzed Cross‐Coupling Reaction of Diazo Compounds and Vinyl Boronic Acids: An Approach to 1,3‐Diene Compounds.

AbstractA novel approach to 1,3‐dienes having one double bond in a carbocyclic or oxacyclic ring by Pd‐catalyzed coupling of α‐diazoketones and lactones with vinyl boronic acids is presented.

ChemInform Abstract: Stereoselective Formation of Trisubstituted Vinyl Boronate Esters by the Acid‐Mediated Elimination of α‐Hydroxyboronate Esters.

The copper-catalyzed diboration of ketones followed by an acid-catalyzed elimination leads to the formation of 1,1-disubstituted and trisubstituted vinyl boronate esters with moderate to good yields and selectivity. Addition of tosic acid to the crude diboration products provides the corresponding vinyl boronate esters upon elimination. The trisubstituted vinyl boronate esters are formed as the (Z)-olefin isomer, which was established by subjecting the products to a Suzuki–Miyaura coupling reaction to obtain alkenes of known geometry.

Enantioselective Diboration of Vinyl Boronates

Enantioselective Diboration of Vinyl Boronates

Heck-Mizoroki coupling of vinyliodide and applications in the synthesis of dienes and trienes.

Vinyliodide reacts chemoselectively under Heck-Mizoroki conditions with terminal alkenes, including vinylboronate esters, to give dienes. The resulting dienylboronates undergo Suzuki-Miyaura couplings with aryl, heteroaryl and alkenyl halides to access dienes and trienes.

Radical isomerization of borylated allylic sulfones

We report a preliminary study of the radical isomerization of borylated allylic sulfones to their more thermodynamically stable isomers. This reaction is important as it provides access to structurally unique vinyl boronates not easily accessible by other means.

Enantiomerically enriched tris(boronates): readily accessible conjunctive reagents for asymmetric synthesis.

The catalytic enantioselective diboration of vinyl boronate esters furnishes chiral tris(boronates) in a selective fashion. Subsequent deborylative alkylation occurs in a diastereoselective fashion, both for intermolecular and intramolecular processes.

Stereoselective formation of trisubstituted vinyl boronate esters by the acid-mediated elimination of α-hydroxyboronate esters.

The copper-catalyzed diboration of ketones followed by an acid-catalyzed elimination leads to the formation of 1,1-disubstituted and trisubstituted vinyl boronate esters with moderate to good yields and selectivity. Addition of tosic acid to the crude diboration products provides the corresponding vinyl boronate esters upon elimination. The trisubstituted vinyl boronate esters are formed as the (Z)-olefin isomer, which was established by subjecting the products to a Suzuki–Miyaura coupling reaction to obtain alkenes of known geometry.

Reactivity and selectivity of boron-substituted alkenes in the Diels-Alder reaction with cyclopentadiene. A study of the electron charge density and its Laplacian.

The effect of the nature of the boron moiety upon the reactivity and the selectivity of a variety of vinylboron dienophiles (1-12) in the Diels-Alder (DA) reaction was investigated using density functional theory and the quantum theory of atoms in molecules. The calculated reactivity of the dienophiles decreases in the order vinylborane (1) > dihalovinylboranes (2-4) > dialkylvinylboranes (5-7) ≈ vinyl boronic acid (8) > vinylboronates (9, 10) > vinyl MIDA boronate (11) ≈ vinyltrifluoroborate (12). The DA reactions of 1-7 were slightly endo-selective due to the stronger C6-B secondary orbital interaction in the endo transition structures (TSs) evaluated by the C6|B delocalization index. In the TSs of 5 and 7, a combination of electronic and steric factors reduce the endo selectivity. The moderate exo selectivity calculated for the DA reactions of boronates 8-11 was attributed mainly to the hydrogen bond between the oxygen atom of boronate moieties and one of the acidic hydrogens of the methylene of cyclopentadiene in the exo TSs, which also reduces the ability of the oxygen lone pairs to donate electron density into the vacant boron orbital. Interestingly, the cooperative effect between the two hydrogen bonds in the exo TS of the DA reaction of vinyltrifluoroborate (12) determines the almost exclusive exo selectivity predicted for this DA reaction. We propose that the relative reactivities of the dienophiles can be estimated by the charge density (ρr) and its Laplacian (∇(2)ρr) at the (3,+1) critical point in the topology of ∇(2)ρr, evaluated at the reactant molecules in the ground state. The profiles of the several topological parameters along the reaction are affected by the nature of the substituents attached to the boron atom and by the mode of addition (endo and exo) in the DA reactions.

Synthesis and Dual D<sub>2</sub> and 5-HT<sub>1A</sub> Receptor Binding Affinities of 7-piperazinyl and 7-piperidinyl-3,4-dihydroquinazolin-2(1H)-ones

A series of new 7-piperazinyl and 7-piperidinyl-3,4-dihydroquinazolin-2(1H)-ones has been synthesized. The described compounds are structurally related to adoprazine, a potential atypical antipsychotic bearing potent D2 receptor antagonist and 5-HT1A receptor agonist properties. Suitably modified aryl bromides were prepared and condensed with tert-butyl piperazine-1-carboxylate to afford the advanced intermediate piperazinyl-3,4-dihydroquinazolin-2(1H)-one. Likewise Suzuki-Miyaura cross-coupling reaction of cyclic vinyl boronate with appropriate aryl bromides rendered piperidinyl-3,4-dihydroquinazolin-2(1H)-one. The reductive amination of the piperazinyl and piperidinyl-3,4- dihydroquinazolin-2(1H)-ones with suitably designed biarylaldehydes accomplished the synthesis of these title compounds. The described compounds were screened for D2 and 5-HT1A receptors binding affinities. The structure-activity relationship studies revealed that cyclopentenylpyridine and cyclopentenylbenzyl groups contribute significantly to the dual D2 and 5-HT1A receptor binding affinities of these compounds.

ChemInform Abstract: Chemo‐ and Diastereoselective Tandem Dual Oxidation of B(pin)‐Substituted Allylic Alcohols: Synthesis of B(pin)‐Substituted Epoxy Alcohols, 2‐Keto‐anti‐1,3‐diols and Dihydroxy‐tetrahydrofuran‐3‐ones.

A novel retrosynthetic disconnection for the stereoselective preparation of α,α′-dioxygenated carbonyl compounds is disclosed. Herein we report a method to divert the oxidation of vinyl boronate esters from the B–C bond to the CC bond, resulting in a new stereoselective class of oxidation products from vinyl boronate esters. Treatment of 2-B(pin)-substituted allylic alcohols with catalytic OV(acac)2 and TBHP resulted in a highly chemo- and diastereoselective directed epoxidation to provide B(pin)-substituted epoxy alcohols (55–96% yield, dr > 20 : 1). In the case of B(pin)-substituted bis-allylic alcohols, highly substituted bis-epoxy alcohols with five contiguous stereocenters were obtained (dr > 20 : 1). Furthermore, the difference in reactivity between allylic alcohols and 2-B(pin)-substituted allylic alcohols towards epoxidation enabled the selective oxidation of the allylic alcohol in the presence of TBHP and VO(acac)2. The reactivity difference between the two allylic alcohols suggests CCB(pin) to be more electron deficient than CC(alkyl). The B(pin)-substituted epoxy alcohols are also useful synthetic intermediates. Tandem vanadium catalyzed epoxidation of the 2-B(pin)-substituted allylic and bis-allylic alcohols with excess TBHP generated the intermediate epoxides and bis-epoxides, respectively. Subsequent addition of NaOH resulted in the oxidation of the B–C bond of the B(pin)-substituted epoxides to afford 2-keto-anti-1,3-diols (60–83% yield) and epoxide-substituted 2-keto-anti-1,3-diols (60–78% yield, dr > 20 : 1). The latter underwent a novel facile acid-mediated cyclization to furnish fully substituted dihydroxy-tetrahydrofuran-3-ones (65–91% yield, dr > 20 : 1). Such compounds are difficult to efficiently access via conventional synthetic methods.

Total Synthesis of (±)-Distomadines A and B

The total synthesis of distomadines A and B, two structurally unique tetracyclic quinolines, is described. The route features a three-step process to access the pyranoquinoline butenolide rings via a Suzuki cross coupling of a 5-bromo-4-methoxycarbonylmethoxyquinoline with a vinyl boronate, followed by an α-ketohydroxylation and double cyclization by intramolecular aldol condensation and lactonization. Subsequent manipulation of the side chain to introduce the guanidine fragment completed the synthesis of distomadine B, whereas the distomadine A congener resulted from decarboxylation of a late-stage intermediate.

ChemInform Abstract: Haloboration of Internal Alkynes with Boronium and Borenium Cations as a Route to Tetrasubstituted Alkenes.

Vinyl boronates are extremely useful precursors, especially for the formation of new C–C bonds by cross-coupling and conjugate addition reactions.1, 2 Although alkyne hydroboration is a powerful synthetic route,3, 4 it is not applicable to the synthesis of trisubstituted vinyl boronates. Thus, alternative regio- and stereospecific methods are needed, particularly for subsequent use in the formation of tetrasubstituted alkenes,5–7 as the production of these important biologically active compounds as single isomers by classical methods is challenging.8 One simple approach to trisubstituted vinyl boronates is the functionalization of internal alkynes by metal-catalyzed 1,2-carboboration9–13 and 1,1-carboboration.14 The introduction of two selectively transformable moieties onto an internal alkyne should enable ready access to tetrasubstituted alkenes by successive cross-coupling reactions. Significant progress has been made in this area, particularly in the dimetalation of internal alkynes to provide two nucleophilic sites of distinct reactivity.15–19 The haloboration of internal alkynes is an attractive alternative to dimetalation, as it generates ambivalent synthetic intermediates that contain both a nucleophilic and an electrophilic position.20 These synthetic intermediates are ideally suited for the diversity-oriented synthesis of tetrasubstituted alkenes. To date, the application of alkyne haloboration with boron trihalides (BX3) has been limited to terminal alkynes, and has proved an effective route to produce trisubstituted alkenes with excellent regio- and stereoselectivity.21–25 The haloboration of internal alkynes is unsuccessful with BCl3, and it is either slow25 or produces isomeric mixtures susceptible to B–C bond cleavage when BBr3 is used.21, 26 Recent calculations found that the haloboration of internal alkynes with BCl3 is endothermic, but as the Lewis acidity of BX3 increases (Cl<Br<I), haloboration becomes exothermic, and the energy of the key transition state is also reduced.27 This result suggested that an increase in the electrophilicity at boron beyond that of BX3 would facilitate the haloboration of internal alkynes.

Cross-Metathesis Approach for Stereocontrolled Synthesis of the C1–C15 Fragment of Rhizopodin

The C1–C15 fragment of rhizopodin was synthesized through either Suzuki coupling reaction of vinyl iodide and vinyl boronate or cross-metathesis of a terminal olefin and a diene adduct in the presence of Hoveyda–Grubbs II catalyst.

Haloboration of internal alkynes with boronium and borenium cations as a route to tetrasubstituted alkenes.

Hail boration! 2-Dimethylaminopyridine-ligated dihaloborocations [X2B(2-DMAP)](+) with a strained four-membered boracycle were used for the haloboration of terminal and dialkyl internal alkynes (see scheme). Esterification then provided vinyl boronate esters as useful precursors to tetrasubstituted alkenes. Following mechanistic studies, the scope of the haloboration was expanded simply by variation of the amine. Pin = 2,3-dimethyl-2,3-butanedioxy.